ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. Insulin-like growth factor-2 (IGF-2) is an important autocrine and paracrine growth factor which may induce cell proliferation and inhibit cell apoptosis leading to the transformation of normal cells into malignant cells. This study aimed to evaluate the possible roles of IGF-2, insulin-like growth factor-2 receptor (IGF-2R), and insulin receptor substrate (IRS)-2 genes polymorphisms in susceptibility and clinicopathological features of HCC in Egyptian population. MATERIALS AND METHODS: Four hundred and twenty-six HCC patients and 334 controls were enrolled in the study. Polymorphisms of IGF-2+3580, IGF-2+3123, IGF-2R 1619, and IRS-2 1057 gene were detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IGF-2 were determined using ELISA. RESULTS: Serum IGF-2 levels were significantly lower in HCC patients than in healthy controls. IGF-2+3580 AA genotype, IGF-2+3123 GG genotype or G allele, IRS-2 1057 DD genotype and D allele were significantly associated with HCC risk. The combination of IGF-2+3580 AA homozygosity and IGF-2R 1619 GG homozygosity presented a significant protective effect against HCC (OR=0.16,95% CI=0. 08-0.34, P=0. 005). Serum IGF-2 concentrations were significantly increased in HCC patients with the IGF-2+3580 AA genotype. We also observed that increased alpha-fetoprotein (AFP), Child-Pugh grade, tumor size, and number of malignant lesions were accompanied by a significant increase of serum IGF-2 mean values of in HCC patients. CONCLUSION: IGF-2, IGF-2R, and IRS-2 genes polymorphisms and their combinations are associated with risk of HCC.
Subject(s)
Carcinoma, Hepatocellular/pathology , Genetic Predisposition to Disease , Insulin Receptor Substrate Proteins/genetics , Insulin-Like Growth Factor II/genetics , Liver Neoplasms/pathology , Polymorphism, Genetic , Receptor, IGF Type 2/genetics , Adult , Base Sequence , Carcinoma, Hepatocellular/genetics , Case-Control Studies , DNA Primers , Egypt , Electrophoresis, Agar Gel , Enzyme-Linked Immunosorbent Assay , Humans , Insulin Receptor Substrate Proteins/blood , Insulin-Like Growth Factor II/metabolism , Liver Neoplasms/genetics , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Receptor, IGF Type 2/bloodABSTRACT
Lupus nephritis includes a wide range of parenchymal injuries and severity. Better predictors to outcome are needed for patients newly diagnosed with lupus nephritis, so that an appropriate management strategy may be selected. This study aimed to determine whether the ratio of hepatocyte growth factor (HGF) to transforming growth factor beta 1 (TGF beta1) in lupus nephritis could be a prognostic factor for response to therapy with cyclophosphamide and steroids at six months. Also, to determine whether a simple automated system for objective scoring of biopsies of lupus nephritis could be a prognostic factor for response to therapy with cyclophosphamide and steroids at 6 months. Consequently, renal biopsy findings and clinical parameters of thirty parasites-free patients with new onset lupus nephritis were recorded. Histopathologic, clinical, immune-histochemical and morphometric data at baseline served to define the predictive value for outcome after 6 months of therapy. The results showed a significant positive relationship between response to therapy and HGF IS (P= 0.007), HGF ES (P= 0.026), HGF IS/ TGFbeta1 IS ratio (P= 0.022) and HGF ES/ TGFbeta1 ES ratio (P= 0.001). A significant inverse relationship was proved between response to therapy and TGFbeta1 IS (P= 0.025) as well as TGFbeta1 ES (P= 0.017). Also, a significant inverse relationship was present between response to therapy and nuclear index, tubular index and matrix index (P = 0.03, 0.03 and 0.029 respectively).
